Details About Overdose or Poisoning Generic Salt :: Leucovorin Calcium
Drug Pharmacology ::
I. Pharmacology. Leucovorin(folinic acid or citrovorum factor) is a metabolically functional formof folic acid. Unlike folic acid, leucovorin does not require reductionby dihydrofolate reductase, and therefore it can participate directlyin the one-carbon transfer reactions necessary for purine biosynthesisand cellular DNA and RNA production. In animal models of methanolintoxication, replacement of a deficiency of leucovorin and folic acidcan reduce morbidity and mortality by catalyzing the oxidation of thehighly toxic metabolite formic acid to nontoxic products. However,there is no evidence that administration of these agents in the absenceof a deficiency is effective.
Drug Indications ::
Folic acid antagonists (eg, methotrexate, trimethoprim, and pyrimethamine). Note: Leucovorintreatment is essential because cells are incapable of utilizing folicacid owing to inhibition of dihydrofolate reductase.
Methanol poisoning. Leucovorin is an alternative to folic acid.
Drug Contra-Indications ::
III. Contraindications. No known contraindications.
Drug Adverse Effects ::
IV. Adverse effects
Allergic reactions as a result of prior sensitization have been reported.
Hypercalcemia from the calcium salt may occur (limit infusion rate to 16 mL/min).
Use in pregnancy. FDAcategory C (indeterminate). This does not preclude its acute,short-term use in a seriously symptomatic patient (see Table III–1).
Drug Lab Interactions ::
Drug or laboratory interactions. Leucovorin bypasses the antifolate effect of methotrexate.
Drug Dose Management ::
Dosage and method of administration
Methotrexate poisoning. Note: Efficacy depends on early administration; the drug should be given within 1 hour of poisoning if possible.Administer intravenously a dose equal to or greater than the dose ofmethotrexate. If the dose is large but unknown, administer 75 mg(children, 10 mg/m2/dose) and then 12 mg every 6 hours forfour doses. Serum methotrexate levels can be used to guide subsequentleucovorin therapy (Table III–9). Do not use oral therapy.
Other folic acid antagonists. Administer 5–15 mg/day IM, IV, or PO for 5–7 days.
Methanol poisoning. Foradults and children, give 1 mg/kg (up to 50–70 mg) IV every 4 hours forone to two doses. Oral folic acid is given thereafter at the samedosage every 4–6 hours until resolution of symptoms and adequateelimination of methanol from the body (usually 2 days). Althoughleucovorin could be used safely for the entire course of treatment, itis no more effective than folic acid and its cost does not justify suchprolonged use in place of folic acid.
Drug Chemical Formulations ::
Parenteral. Leucovorincalcium (Folinic Acid, Citrovorum Factor), 3- and 10-mg/mL vials; 50,100, and 350 mg for reconstitution (use sterile water rather than thediluent provided, which contains benzyl alcohol).
Oral. Leucovorin calcium (various), 5-, 15-, and 25-mg tablets.
The suggested minimum stocking level to treat a 70-kg adult for the first 24 hours is two 100-mg vials or one 350-mg vial.
Table III–9. Leucovorin Dose Determination (after the First 24 Hours)
Methotrexate Concentration (mcmol/L) Hours After Methotrexate Exposure Leucovorin Dosea (Adults and Children) 0.1–12410–15 mg/m2 every 6 hours for 12 doses
1–52450 mg/m2 every 6 hours until the serum level is less than 0.1 mcmol/L
5–1024100 mg/m2 every 6 hours until the serum level is less than 0.1 mcmol/L
Reference: Methotrexate Management, in Rumack BH et al (eds.); Poisindex. Denver, 1989.
aIfserum creatinine increases by 50% in the first 24 hours aftermethotrexate, increase the dose frequency to every 3 hours until themethotrexate level is less than 5 mcmol/L